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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1982
Reference Type:
secondary source
Title:
European Union Risk Assessment Report - 1,2,4-Trichlorobenzene
Author:
European Commission - European Chemicals Bureau
Year:
2003
Bibliographic source:
Office for Official Publications of the European Communities

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Analytical purity not reported. Acclimation period not reported. Body weights were not reported.
GLP compliance:
no
Remarks:
GLP was not mandatory at the time of the study
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1, 2, 4-trichlorobenzene
- Physical state: liquid
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 9 (males) - 14 (females) weeks
- Weight at study initiation: 159-173 g (males); 159-172 g (females)
- Fasting period before study: the animals were fasted from 16 to 4 hours before the dosing
- Housing: Rats were housed in number of 5 per cage in Makrolon cages type III
- Diet (e.g. ad libitum): Altromin R 1324, Altromin GmbH, Lage, Germany
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 60 ± 5%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light (7am/7pm)



IN-LIFE DATES: From: April To: July 1981

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: cremophore/tap water mixture (1 : 4)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
630-3100 mg/kg
No. of animals per sex per dose:
5
Control animals:
other: not applicable
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice per day and once on weekends and holidays. The animals were weighed at the moment of the exposure, after 1 week, and at the end of the 14-day oberservation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology analysis
Statistics:
The calculation of the LD50 with the confidence interval for p <0.05 was performed with the Probit analysis according to Fink und Hund (Arzneim.-Forsch. 15:1965, 624)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
930 mg/kg bw
95% CL:
>= 840 - <= 1 050
Remarks on result:
other: Slope=9.11
Mortality:
The deaths occurred during the first 3 days of the treatment
Clinical signs:
The oral single doses from 730 to 3100 mg/kg provoked the following poisoning symptoms: worsening of the general conditions, sedation, necrosis, side-prone position.
The symptoms appeared circa 5 minutes after the exposure and were visible until 5 days post-exposure
Body weight:
Not reported
Gross pathology:
In the section of deceased male and female animals were noted alterations of the stomach and intestine mucous membrane, and gastric bleeding .
The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1.0 and 1.25 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

Any other information on results incl. tables

Male

Dose

mg/kg

Number of dead animals

Animals with symptoms

Total number of animals employed

Time of death

630

0

0

5

 

730

1

5

5

2ndday

800

3

5

5

2nd-3rdday

1000

3

5

5

2ndday

1250

5

5

5

24 hours-2ndday

1600

5

5

5

24 hours

3100

5

5

5

24 hours

Female

Dose

mg/kg

Number of dead animals

Animals with symptoms

Total number of animals employed

Time of death

630

0

0

5

 

730

0

5

5

 

800

2

5

5

3rdday

1000

3

5

5

2nd-3rdday

1250

3

5

5

24 hours-2ndday

1600

5

5

5

24 hours-2ndday

3100

5

5

5

24 hours

 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information R22, Harmful if swallowed Criteria used for interpretation of results: EU
Executive summary:

Bomhard, 1981:

Groups of 5 rats of each sex with starting weights between 159 g and 173 g were given 1,2,4-trichlorobenzene (630-3100 mg/kg) by gavage according to OECD guideline 401 with deviations (Analytical purity not reported. Air changes not reported. Acclimation period not reported.Body weights not reported).

The LD50 was 930 mg/kg with 95% confidential limit of 840-1050.

The deaths occurred during the first 3 days of the treatment.

The oral single doses from 730 to 3100 mg/kg provoked the following poisoning symptoms: worsening of the general conditions, sedation, necrosis, side-prone position.

In the section of deceased male and female animals were noted alterations of the stomach and intestine mucous membrane, and gastric bleeding.

The liver had a localized clay colour and showed clear lobe markings. At the end of the test in the dissected male and female animals dosed with 1000 and 1250 mg/kg were observed slight alterations of the stomach. All other animals were examined macroscopically unremarkable.

On the basis of theses findings it is possible to classify 1,2,4 -trichlorobenzene as Xn R22, harmful if swallowed (EU classification), and Acute Tox. 4, H302 (according to GHS).